Enhancement of periodontal tissue regeneration by locally controlled delivery of insulin-like growth factor-I from dextran-co-gelatin microspheres
Enhancement of periodontal tissue regeneration by locally controlled delivery of insulin-like growth factor-I from dextran-co-gelatin microspheres
复制标题
通过从葡聚糖-明胶微球中局部控制胰岛素样生长因子-I 的输送来增强牙周组织再生。
DOI：
10.1016/j.jconrel.2006.05.014
复制
发表时间：
2006-08-28
影响因子：
10.8
通讯作者：
Jin, Yan
中科院分区：
文献类型：
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作者：
Chen, Fa-ming;Zhao, Yi-min;Jin, Yan
本研究旨在设计一种新型的基于葡聚糖和明胶生物材料的水凝胶微球，并探讨从葡聚糖-明胶水凝胶微球(DG-MP)局部控制释放IGF-I是否有助于促进牙周组织的再生。将明胶与甲基丙烯酸缩水甘油酯(GMA)衍生的右旋糖苷(DX-GMA)协同作用，合成了具有水凝胶性质的DG-MP微球，其交联密度可由DX-GMA的取代度(DS，每100个吡喃葡萄糖残基中的甲基丙烯酸酯数目)控制。本研究从明胶和Dex-GMA(取代度分别为4.7、6.3和7.8)制备了三种DG-MP(DG-MP4.7、DG-MP6.3和DG-MP7.8)，并对其溶胀和降解性能、药物释放动力学和促进组织再生的生物学能力进行了表征。通过在带正电荷的IGF-I水溶液中溶胀，蛋白质可以通过与带负电荷的酸性明胶的多离子络合作用被包裹在DG-MP中。DX-GMA的取代度对DG-MP的形态和大小没有明显的影响，三种DG-MP在PBS缓冲液中的释放和降解性能也没有显著差异。然而，在含有葡聚糖酶的PBS中，高取代度的DX-GMA可以显著降低微球的溶胀，延长其降解时间，减少IGF-I的突释，其中缓释型微球(DG-MP7.8)的IGF-I释放可维持28d以上，并实现了有效的蛋白质释放动力学，没有明显的突释，但在首次突释后保持了相对恒定的释放。DG-MP中的IGF-I在4周或8周内在牙周缺损处的新骨形成明显多于IGF-I直接在血块中的新骨形成(P<；0.01)。DG-MP7.8组新生牙周组织的高度、新骨和新牙骨质在分叉区裸露根面的百分率均高于其他两组(P<；0.05)。DG-MP7.8组再生牙周膜(PDL)宽度适中，Sharpey纤维规则，牙槽骨重建良好。这些综合结果表明，通过调节DX-GMA的取代度和DG-MP的交联度可以实现有效的释放动力学，而缓释型DG-MP的局部控释IGF-I可能成为牙周组织再生的一种新的治疗策略。(C)2006爱思唯尔B.V.保留所有权利。
The present work focused on the design of novel hydrogel microspheres based on both dextran- and gelatin-derived biomaterials, and discussed whether locally controlled delivery of IGF-I from dextran-co-gelatin hydrogel microspheres (DG-MP) was useful for periodontal regeneration enhancement. Microspheres were synthesized when gelatin was cooperating with glycidyl methacrylate (GMA) derivatized dextrans (Dex-GMA) and the resultant DG-MP with a hydrogel character of which the cross-linking density could be controlled by the degree of substitution (DS, the number of methacrylates per 100 glucopyranose residues) of Dex-GMA. In this study, three types of DG-MP (DG-MP4.7, DG-MP6.3 and DG-MP7.8) obtained from gelatin and Dex-GMA (differing in DS: 4.7, 6.3 and 7.8 respectively) were prepared and characterized by swelling and degradation properties, drug release kinetics and biological capability in promoting tissue regeneration. By swelling in aqueous positively charged IGF-I solutions, the protein could be encapsulated in DG-MP by polyionic complexation with negatively charged acidic gelatin. No obvious influence of Dex-GMA's DS on DG-MP's configuration and size was observed, and the release and degraded properties showed no significant difference between three types of DG-MP in PBS buffer either. However, high DS of Dex-GMA could lower microsphere's swelling, prolong its degraded time and minimize IGF-I burst release markedly in dextranase-containing PBS, where IGF-I release from a slow release type of microspheres (DG-MP7.8) could be maintained more than 28 days, and an effective protein release kinetics without a significant burst but a relevantly constant release after the initial burst was achieved. IGF-I in DG-MP resulted in more new bone formation in the periodontal defects within 4 or 8 weeks than IGF-I in blood clot directly did (P < 0.01). The observed newly formation of periodontal tissues including the height and percentage of new bone and new cementum on the denuded root surfaces of the furcation area in DG-MP7.8 group were more than that in other groups (P < 0.05). The adequate width of regenerative periodontal ligament (PDL), regular Sharpey's fibers and alveolar bone reconstruction could be observed only in DG-MP7.8 group. These combined results demonstrate that effective release kinetics can be realized by adjusting the DS of Dex-GMA and followed cross-linking density of DG-MP, and that locally controlled delivery of IGF-I from slow release type of DG-MP may serve as a novel therapeutic strategy for periodontal tissue regeneration. (c) 2006 Elsevier B.V. All rights reserved.